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  • Gyllenberg, A, et al. (författare)
  • Age-dependent variation of genotypes in MHC II transactivator gene (CIITA) in controls and association to type 1 diabetes
  • 2012
  • Ingår i: Genes and Immunity. - Stockholm : Nature Publishing Group. - 1476-5470 .- 1466-4879. ; 13:8, s. 632-640
  • Tidskriftsartikel (refereegranskat)abstract
    • The major histocompatibility complex class II transactivator (CIITA) gene (16p13) has been reported to associate with susceptibility to multiple sclerosis, rheumatoid arthritis and myocardial infarction, recently also to celiac disease at genome-wide level. However, attempts to replicate association have been inconclusive. Previously, we have observed linkage to the CIITA region in Scandinavian type 1 diabetes (T1D) families. Here we analyze five Swedish T1D cohorts and a combined control material from previous studies of CIITA. We investigate how the genotype distribution within the CIITA gene varies depending on age, and the association to T1D. Unexpectedly, we find a significant difference in the genotype distribution for markers in CIITA (rs11074932, P=4 × 10(-5) and rs3087456, P=0.05) with respect to age, in the collected control material. This observation is replicated in an independent cohort material of about 2000 individuals (P=0.006, P=0.007). We also detect association to T1D for both markers, rs11074932 (P=0.004) and rs3087456 (P=0.001), after adjusting for age at sampling. The association remains independent of the adjacent T1D risk gene CLEC16A. Our results indicate an age-dependent variation in CIITA allele frequencies, a finding of relevance for the contrasting outcomes of previously published association studies.
  • Jobory, Ammar, et al. (författare)
  • Hip precautions not meaningful after hemiarthroplasty due to hip fracture. Cluster-randomized study of 394 patients operated with direct anterolateral approach.
  • 2019
  • Ingår i: Injury. - : Elsevier. - 1879-0267 .- 0020-1383. ; 50:7, s. 1318-1323
  • Tidskriftsartikel (refereegranskat)abstract
    • We aimed to compare two treatment regimes, one with and one without postoperative precautions in hemiarthroplasty patients, in terms of dislocation rate and patient-reported outcome. Direct lateral approach was used.394 patients were included in a cluster-randomized study 2010-2014. Depending on which ward they were admitted to, they were allotted to free rehabilitation (non-precaution group, NPG, n = 226) or our conventional regime with precautions and mandatory assistive equipment (precaution group, PG, n = 168). Patients were followed during hospital stay, at 6 weeks (postal questionnaire), 3 month (visit) and 6 months (reading of medical records) by means of function tests, health-related quality of life (EQ-5D) and other patient-reported outcome measures (PROM).One patient in each group had dislocation(s). We found no statistically significant differences regarding in-hospital-mortality, severe adverse events, EQ5D index or other PROM. In the NPG, rehabilitation personnel had significantly shorter work effort during hospital stay (p < 0.001). 7 in the NPG and 13 of the PG had reoperations (p = 0.038), 4 and 8 had deep infections, 3 and 5 periprosthetic fractures.Rehabilitation precautions are not needed for preventing dislocation when direct lateral approach is used. Without precautions, rehabilitation personnel implement significantly shorter work effort during hospital. We found no statistically significant differences regarding PROM and complications except for somewhat more reoperations in total in the precaution group.
  • Söreskog, Emma, et al. (författare)
  • Risk of major osteoporotic fracture after first, second and third fracture in Swedish women aged 50 years and older
  • 2020
  • Ingår i: Bone. - : Elsevier. - 8756-3282 .- 1873-2763. ; 134
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Osteoporosis affects approximately one in five European women and leads to fragility fractures, which result in poor health, social and economic consequences. Fragility fractures are a strong risk factor for subsequent major osteoporotic fracture (MOF), with risk of MOF being elevated in the 1–2 years following an earlier fracture, a concept described as “imminent risk”. This study examines risk of subsequent MOF in patients with one, two or three prior fractures by age and type of fracture. Methods: In this retrospective, observational cohort study, Swedish women aged ≥50 years with ≥1 any clinical fragility fracture between July 1, 2006 and December 31, 2012 were identified from Sweden's National Patient Register. Each patient was age- and sex-matched to three controls without history of fracture. Group 1 women included those with one fragility fracture during the study period; Group 2 included those with two fragility fractures; and Group 3 included those with three fragility fractures. “Index fracture” was defined as the first fracture during the study period for Group 1; the second for Group 2; and the third for Group 3. Patients in each cohort and matched controls were followed for up to 60 months or until subsequent MOF (hip, vertebra, forearm, humerus), death or end of data availability. Results: 231,769 women with at least one fracture were included in the study and therefore constituted Group 1; of these, 39,524 constituted Group 2 and of those, 7656 constituted Group 3. At five years, cumulative incidence of subsequent MOF was higher in patients with a history of fracture as compared to controls (Group 1: 20.7% vs 12.3%; Group 2: 32.0% vs 15.3%). Three-year cumulative incidence for Group 3 was 12.1% (vs 10.7% for controls). After adjusting for baseline covariates, risk of subsequent MOF was highest within 0–24 months following an index fracture, then decreased but remained elevated as compared to controls. Having two prior fractures, vertebral fractures and younger age at time of index fracture were associated with greater relative risk. Conclusions: Women with a history of osteoporotic fracture are at increased risk of subsequent fracture, which is highest during the first 24 months following a fracture. Younger women and those with vertebral fractures are at greatest relative risk, suggesting that treatment should target these patients and be timely enough to impact the period of imminent risk.
  • Åkeson, Pia Karlsland, et al. (författare)
  • Vitamin D intervention and bone : A randomized clinical trial in fair- and dark-skinned children at northern latitudes
  • 2018
  • Ingår i: Journal of Pediatric Gastroenterology and Nutrition. - : Lippincott Williams & Wilkins. - 0277-2116 .- 1536-4801. ; 67:3, s. 388-394
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: The aim of the study was to evaluate vitamin D status and effects of vitamin D intervention on bone mineral density (BMD) and content (BMC) in children with fair and dark skin in Sweden during winter. Methods: In a 2-center prospective double-blinded randomized intervention study 5- to 7-year-old children (n=206) with fair and dark skin in Sweden (55°N-63°N) received daily vitamin D supplements of 25μg, 10μg, or placebo (2μg) during 3 winter months. We measured BMD and BMC for total body (TB), total body less head (TBLH), femoral neck (FN), and spine at baseline and 4 months later. Intake of vitamin D and calcium, serum 25- hydroxy vitamin D (S-25[OH]D), and related parameters were analyzed. Results: Despite lower S-25(OH)D in dark than fair-skinned children, BMD of TB (P=0.012) and TBLH (P=0.002) and BMC of TBLH (P=0.04) were higher at baseline and follow-up in those with dark skin. Delta (Δ) BMD and BMC of TB and TBLH did not differ between intervention and placebo groups, but FN-BMC increased more among dark-skinned children in the 25μg (P=0.038) and 10μg (P=0.027) groups compared to placebo. We found no associations between Δ S-25(OH)D, P-parathyroid hormone, P-alkaline phosphatase, and D BMD and BMC, respectively. Conclusions: BMD and BMC remained higher in dark- than fair-skinned children despite lower vitamin D status. Even though no difference in general was found in BMD or BMC after vitamin D intervention, the increase in FN-BMC in dark-skinned children may suggest an influence on bone in those with initially insufficient vitamin D status.
  • Brändström, Helena, et al. (författare)
  • Single nucleotide polymorphisms in the human gene for osteoprotegerin are not related to bone mineral density or fracture in elderly women
  • 2004
  • Ingår i: Calcified Tissue International. - : Springer. - 0171-967X .- 1432-0827. ; 74:1, s. 18-24
  • Tidskriftsartikel (refereegranskat)abstract
    • Osteoprotegerin (OPG), a secreted member of the tumor necrosis factor receptor family, is a potent inhibitor of osteoclast activation and differentiation. In animal models OPG prevents bone loss, and in humans bone resorption can be reduced by injections of OPG. OPG may also play a role in cardiovascular disease since mice lacking the OPG gene display arterial calcification. In a screening effort of the OPG gene, we recently discovered a single nucleotide polymorphism in the promoter region of OPG (T950C), and reported an association with vascular morphology and function in 59 healthy individuals. Due to the pronounced effect of OPG on bone turnover, the present study was conducted to investigate whether OPG polymorphisms are also associated with bone mineral density or with fracture. The relationship between single nucleotide polymorphisms in the promoter region of OPG (T950C) and the first intron (C1217T), and bone mineral density, measured by DXA in the hip or spine or ultrasound of the heel, was investigated in the Malmö OPRA-study of 1044 women, all 75 years old. The possible relation to fracture incidence was also analyzed. Among the 858 and 864 individuals respectively, genotyped, no significant associations between the investigated single nucleotide polymorphisms and bone mineral density measurements (T950C P = 0.50-0.64, C1217T P = 0.51-1.00), quantitative ultrasound measurements of the calcaneus, or fractures (T950C P = 0.61-0.66, C1217T P = 0.14-0.33) were found. Thus, our results show that polymorphisms in the OPG gene, one of which has previously been found to be associated with cardiovascular morphology and function, are not associated with bone mineral density in elderly Swedish women.
  • Buchebner, David, et al. (författare)
  • Longitudinal Assessment of PTH in Community-Dwelling Older Women-Elevations Are Not Associated With Mortality
  • Ingår i: Endocrine Pathology. - : Humana Press. - 1046-3976. ; 1:6, s. 615-624
  • Tidskriftsartikel (refereegranskat)abstract
    • Context: In older women, the magnitude of elevated parathyroid hormone (PTH) and its consequence is unclear.Objective: To describe normal PTH profiles over time and the association with mortality.Design and Participants: There were 1044 community-dwelling women in the Malmö Osteoporosis Prospective Risk Assessment cohort (OPRA) who attended baseline (age 75 years). Follow-ups were attended by 715 (age 80 years) and 382 (age 85 years).Main Outcome Measures: PTH, estimated glomerular filtration rate (eGFR), 25-hydroxyvitamin D (25OHD) and mortality.Results: At age 75 years, PTH levels for most (n = 877, 88%) were within the normal reference range (NRR) (i.e., <6.9 pmol/L). Longitudinally, between ages 75 and 80 years, PTH increased in 60% of all women (n = 390) but increases of up to 50% above baseline values (64%; n=250) still resulted in PTH levels within the NRR. These women had lower 25OHD levels (74 vs 83 nmol/L, P = 0.001). Only when increases were >50% was PTH elevated beyond the NRR (mean 7.1 ± 3.3). Here, a pronounced decline in eGFR (56 vs 61 mL/min/1.73 m2, P = 0.002) was found, despite no further changes in 25OHD. Extending the observational period until age 85 years gave similar results. Baseline PTH levels above NRR were associated with mortality (hazard ratio, 1.4; 95% confidence interval (CI), 1.1-1.8; P = 0.007), although not after adjustment for covariates (P = 0.082).Conclusions: Most women remained within normal PTH ranges despite large increases of up to 50%. PTH elevated above normal is not independently associated with mortality; impaired kidney function and low 25OHD status may be more prognostic in the very old.
  • Garg, Gaurav, et al. (författare)
  • Variation in the MC4R Gene Is Associated with Bone Phenotypes in Elderly Swedish Women.
  • 2014
  • Ingår i: PLoS ONE. - : Public Library of Science. - 1932-6203. ; 9:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Osteoporosis is characterized by reduced bone mineral density (BMD) and increased fracture risk. Fat mass is a determinant of bone strength and both phenotypes have a strong genetic component. In this study, we examined the association between obesity associated polymorphisms (SNPs) with body composition, BMD, Ultrasound (QUS), fracture and biomarkers (Homocysteine (Hcy), folate, Vitamin D and Vitamin B12) for obesity and osteoporosis. Five common variants: rs17782313 and rs1770633 (melanocortin 4 receptor (MC4R); rs7566605 (insulin induced gene 2 (INSIG2); rs9939609 and rs1121980 (fat mass and obesity associated (FTO) were genotyped in 2 cohorts of Swedish women: PEAK-25 (age 25, n = 1061) and OPRA (age 75, n = 1044). Body mass index (BMI), total body fat and lean mass were strongly positively correlated with QUS and BMD in both cohorts (r(2) = 0.2-0.6). MC4R rs17782313 was associated with QUS in the OPRA cohort and individuals with the minor C-allele had higher values compared to T-allele homozygotes (TT vs. CT vs.
  • Gerdhem, P., et al. (författare)
  • Association of the collagen type 1 (COL1A 1) Sp1 binding site polymorphism to femoral neck bone mineral density and wrist fracture in 1044 elderly Swedish women
  • 2004
  • Ingår i: Calcified Tissue International. - : Springer. - 0171-967X .- 1432-0827. ; 74:3, s. 264-269
  • Tidskriftsartikel (refereegranskat)abstract
    • Identification of risk factors for osteoporosis has been essential for understanding the development of osteoporosis and related fragility fractures. A polymorphism of the binding site for the transcription factor Sp1 of the collagen I alpha 1 gene (COLIA1) has shown an association to bone mass and fracture, but the findings have not been consistent, which may be related to population differences. The Sp1 polymorphism was determined in 1044 women, all 75 years old, participating in the population-based Osteoporosis Prospective Risk Assessment study in Malmö (OPRA). Bone mineral density, heel ultrasound and all previous fractures were registered. BMD was 2.7% lower in the femoral neck in women carrying at least one copy of the "s" allele ( P = 0.027). There was no difference in bone mass at any other site, weight, BMI or age at menopause. Women with a prevalent wrist fracture (n = 181) had an increased presence of the "s" allele. The odds ratio for prevalent wrist fracture was 2.73 (95% CI 1.1-6.8) for the ss homozygotes and 1.4 (95% CI 1.0-2.0) for the Ss heterozygotes when compared with the SS homozygotes. In conclusion, in this large and homogeneous cohort of 75-year-old Swedish women, there was an association among the Sp1 COLIA1 polymorphism, bone mass, and fracture. The presence of at least one copy of the "s" allele was associated with lower femoral neck BMD and previous wrist fracture and in addition, it was related to an increased risk for wrist fracture.
  • Grundberg, E, et al. (författare)
  • Large-scale association study between two coding LRP5 gene polymorphisms and bone phenotypes and fractures in men
  • 2008
  • Ingår i: Osteoporosis International. - : Springer. - 1433-2965 .- 0937-941X. ; 19:6, s. 829-837
  • Tidskriftsartikel (refereegranskat)abstract
    • Herein we investigated the association between polymorphisms in the LRP5 gene and bone phenotypes and fractures in three large male cohorts based on the rationale that mutations in LRP5 cause severe bone phenotypes. Results showed an association of the Val667Met SNP with spine BMD in 3,800 young and elderly men. INTRODUCTION: The low-density lipoprotein receptor-related protein 5 (LRP5)-Wnt signalling system is of importance for regulating osteoblastic activity, which became clear after findings that inactivating mutations in LRP5 cause osteoporosis. The overall aim of this study was to investigate the association between polymorphisms in the LRP5 gene and bone mineral density (BMD) in three large cohorts of young and elderly men. METHODS: The cohorts used were MrOS Sweden (n = 3014, aged 69-81 years) and MrOs Hong Kong (n = 2000, aged > 65 years) and the Swedish GOOD study (n = 1068, aged 18-20 years). The polymorphisms Val667Met and Ala1330Val were genotyped using a TaqMan assay. RESULTS: When combining the data from the Swedish cohorts in a meta-analysis (n = 3,800), men carrying the 667Met-allele had 3% lower BMD at lumbar spine compared with non-carriers (p < 0.05). The Val667Met SNP was not polymorphic in the Hong Kong population and thus were not included. There were no associations between the Ala1330Val SNP and bone phenotypes in the study populations. No associations between the LRP5 polymorphisms and self-reported fractures were seen in MrOs Sweden. CONCLUSIONS: Results from these three large cohorts indicate that the Val667Met polymorphism but not the Ala1330Val contributes to the observed variability in BMD in the Swedish populations.
  • Grundberg, Elin, et al. (författare)
  • The impact of estradiol on bone mineral density is modulated by the specific estrogen receptor-alpha cofactor retinoblastoma-interacting zinc finger protein-1 insertion/deletion polymorphism.
  • 2007
  • Ingår i: The Journal of clinical endocrinology and metabolism. - 0021-972X .- 1945-7197. ; 92:6, s. 2300-6
  • Tidskriftsartikel (refereegranskat)abstract
    • CONTEXT: Estrogens regulate bone mass by binding to the estrogen receptor (ER)-alpha as well as ER-beta. The specific ERalpha cofactor retinoblastoma-interacting zinc finger protein (RIZ)-1 enhances ERalpha function in the presence of estrogen. OBJECTIVE: The objective of the study was to determine whether a RIZ P704 insertion (+)/deletion (-) (indel) polymorphism modulates the impact of estradiol on bone mineral density (BMD) and study the association between the polymorphism and BMD in elderly subjects. DESIGN: This was a population-based, prospective, and cross-sectional study, the Swedish MrOS Study, and the Malmö OPRA Study, respectively. SETTING: The study was conducted at three academic medical centers: Sahlgrenska Academy in Gothenburg, Malmö University Hospital, and Uppsala University Hospital. PARTICIPANTS: In total, 4058 men and women, aged 69-81 yr, were randomly selected from population registries. MAIN OUTCOME MEASURES: BMD (grams per square centimeter) was measured at femoral neck, trochanter, lumbar spine, and total body. RESULTS: The RIZ P704(+/+) genotype was associated with low BMD in both women (femoral neck, P < 0.001; trochanter, P < 0.01; lumbar spine, P < 0.05; total body, P < 0.01) and men (lumbar spine, P < 0.05). However, the association between the polymorphism and BMD was dependent on estradiol status. The positive correlation between serum estradiol and BMD was significantly modulated by the genotype with a stronger correlation in the P704(+/+) group than the P704(-/-) group (r = 0.19 vs. r = 0.08, P < 0.05). CONCLUSIONS: These large-scale studies of elderly men and women indicate that the ERalpha cofactor RIZ gene has a prominent effect on BMD, and the P704 genotype modulates the impact of estradiol on BMD. Further studies are required to determine whether this polymorphism modulates the estrogenic response to estradiol treatment.
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